In chemical reactions, we often speak about the committed step. In essence, this is an irreversible (ie, highly favorable, downhill, etc) reaction that occurs at some branch point during the synthesis of molecules. After this step, the molecule/intermediate is "committed" or forced to continue down the chosen pathway to the final end product.
In the example below(Scheme 1), reaction #3 is the committed step in the formation of product F.
Scheme 1: Basic representation of a chemical reaction branch point
We can also think of this term as it relates to enzyme-catalyzed reactions. "Commitment to Catalysis" is a quantitative measure of the tendency of the enzyme-substrate complex to proceed onward to product formation as opposed to returning to free enzyme and free substrate. In the case of a high commitment to catalysis, the catalytic rate is much faster than the off rate [kcat >> koff], making it very likely that once the enzyme-substrate complex forms, it will form the desired product (1).
I chose "Commitment to Catalysis" as the name of my blog because of my passion for enzymology. I first developed this obsession as and undergraduate at Macalester college. It was a remarkable realization that enzymes participate in nearly every process within an organism, from immune responses to mechanical transport. Even more unbelievable is that these elegant structures begin from a set of just twenty building blocks. Simply, I was hooked. This blog was created as a way for me to stay up-to-date on current research in the field of chemical biology. It also serves as a way for me to work on science writing that is understandable and accessible.
I chose "Commitment to Catalysis" as the name of my blog because of my passion for enzymology. I first developed this obsession as and undergraduate at Macalester college. It was a remarkable realization that enzymes participate in nearly every process within an organism, from immune responses to mechanical transport. Even more unbelievable is that these elegant structures begin from a set of just twenty building blocks. Simply, I was hooked. This blog was created as a way for me to stay up-to-date on current research in the field of chemical biology. It also serves as a way for me to work on science writing that is understandable and accessible.
2) You say you're studying chemical biology--how is that different from biochemistry?
C2C Blog Post on Chemical Biology
This is how I like to visually simplify the difference:
3) What is epigenetics and why is it important?
If you're still not sure about the caterpillar example, here are a few more analogies that I use in departmental talks to explain the concept of epigenetics.
1) Epigenetic changes are like punctuation.
If we consider DNA to be like the information contained in a paragraph, or even smaller, a sentence, then epigenetics is the punctuation. For example:
This is the one question I am often asked at family functions, by other students, and sometimes even by other chemists who are not familiar with the discipline. The answer: it’s complicated! I explained my interpretation of the difference in one of my early blog posts: Here's the link below.
C2C Blog Post on Chemical Biology
In short, I like Chris Walsh's definition: "The goal [of chemical biology] is a seamless application of chemical principles to decipher complexities in biology and bring scientists trained in chemistry to full engagement on biological projects."
This is how I like to visually simplify the difference:
Often, scientists working at the interface of chemistry and biology must be able to fluidly move between the two disciplines, so having training in either chemical biology or biochemistry helps make the research more elegant.
3) What is epigenetics and why is it important?
Epigenetics (from the Greek prefix epi meaning over or above) literally means "above the genetics." When scientists talk about epigenetics, they are looking for changes in gene expression or cellular phenotype that are not a caused by changes in the underlying DNA. If you think about it, I'm sure you've seen examples of epigenetics in your own life. One example I like to use are caterpillars.
Each cell in a caterpillar contains the same blueprint, the same DNA. Nothing changes in the blueprint before or after getting into the cocoon--so something else must be changing. As it turns out, small chemical groups can be added to DNA, or to proteins that interact with the DNA. These chemical groups can act to turn genes "on" or "off" so that a caterpillar can grow wings at just the right time.
If you're still not sure about the caterpillar example, here are a few more analogies that I use in departmental talks to explain the concept of epigenetics.
If we consider DNA to be like the information contained in a paragraph, or even smaller, a sentence, then epigenetics is the punctuation. For example:
The panda eats shoots and leaves. vs. The panda eats, shoots, and leaves.
Just like different punctuation can change the meaning of the final message, so too can biochemical changes effect what is transcribed/translated from DNA.
2) Epigenetics are like director's notes on a script.
Let's say you are in a theater production of Grease. The director gives the actor playing Danny notes on singing cues, stage directions, prop placement, and other technical details, which Danny writes down in the margins on his copy of the script. The director also has notes for the actress playing Sandy, but these notes are different than the notes on Danny's copy of the script. Whenever someone photocopies Sandy's version of the script, all of the additional notes she took are also copied along with the lines of the play. The same is true for Danny's version.
This is similar to epigenetic regulation. All of the cells in your body have the same script (DNA) but carry different modifications (notes) which turn genes "on" or "off." Just like photocopying, some of these changes can also be inherited, or passed down during cell division.
Epigenetics offers a way for cells to fine-tune control over gene expression and gene regulation. Epigenetics are critical during development and may offer new routes for evolution. They have also been implicated in a number of diseases including obesity, schizophrenia, as well as many different types of cancer. But how exactly do these epigenetic enzymes work? How did they evolve to modify chromatin? How do cells remember these changes?
We like to think of DNA as a book or a script, when really, "[...] it's more like the fold-in from the back of Mad magazine, where folding an image in a particular way created a new picture" (2).
Hopefully, by understanding both gene regulation and epigenetic modifications, we can begin to understand how these processes work together to create life.
References:
1) Purich, D. Enzyme Kinetics: Catalysis and Control. Academic Press: London, 2010.
2) Carey, N. The Epigenetics Revolution: How modern biology is rewriting our understanding of genetics, disease, and inheritance. Columbia University Press: New York, 2012.
